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Drug Resistance and Novel Antimicrobial Agents

Convergent Klebsiella pneumoniae strains belonging to a sequence type 307 outbreak clone combine cefiderocol and carbapenem resistance with hypervirulence

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Article: 2271096 | Received 05 Jul 2023, Accepted 11 Oct 2023, Published online: 31 Oct 2023

Figures & data

Figure 1. Overview of investigated strains and their geno- and phenotypic characteristics. A Metadata, genotypic information, and phenotypic resistance traits of the investigated strains. Minimum inhibitory concentrations for cefiderocol were determined by broth microdilution and interpreted according to EUCAST guidelines. The virulence score was determined using Kleborate, with 0 = negative for yersiniabactin, colibactin and aerobactin, 1 = only yersiniabactin, 2 = only yersiniabactin and colibactin (or colibactin only), 3 = aerobactin (without yersiniabactin or colibactin), and 4 = aerobactin and yersiniabactin (without colibactin). Predictions for siderophore receptors and ompK36 (highlighted in gray) are based on BLAST using PBIO1953 as reference, whereas predictions for carbapenemase genes are based on alignments of sequences from the AMRFinderPlus database [Citation10] (default settings of identity ≥90.0% and coverage ≥50.0%). Mutations in the gene sequence are highlighted in yellow and uncoloured boxes indicate the absence of the respective gene. B Schematic presentation of genetic changes (red) in the cirA gene of cefiderocol-resistant PBIO2003. The single thymine base duplication (arrow) results in a frameshift and a premature stop codon (black). C Cartoon representation of modelled protein structure of the catecholate siderophore receptor CirA. Predicted changes in the architecture of the siderophore receptor in lateral view (left) and top view (right) are coloured in transparent gray. BDH, Neurorehabilitation centre in Greifswald; EE, experimental evolution; FDC, cefiderocol; MIC, minimum inhibitory concentration; n.a., not applicable; R, resistant; S, susceptible; UKSH, University Medical Centre Schleswig-Holstein; UMG, University Medicine Greifswald.

Figure 1. Overview of investigated strains and their geno- and phenotypic characteristics. A Metadata, genotypic information, and phenotypic resistance traits of the investigated strains. Minimum inhibitory concentrations for cefiderocol were determined by broth microdilution and interpreted according to EUCAST guidelines. The virulence score was determined using Kleborate, with 0 = negative for yersiniabactin, colibactin and aerobactin, 1 = only yersiniabactin, 2 = only yersiniabactin and colibactin (or colibactin only), 3 = aerobactin (without yersiniabactin or colibactin), and 4 = aerobactin and yersiniabactin (without colibactin). Predictions for siderophore receptors and ompK36 (highlighted in gray) are based on BLAST using PBIO1953 as reference, whereas predictions for carbapenemase genes are based on alignments of sequences from the AMRFinderPlus database [Citation10] (default settings of identity ≥90.0% and coverage ≥50.0%). Mutations in the gene sequence are highlighted in yellow and uncoloured boxes indicate the absence of the respective gene. B Schematic presentation of genetic changes (red) in the cirA gene of cefiderocol-resistant PBIO2003. The single thymine base duplication (arrow) results in a frameshift and a premature stop codon (black). C Cartoon representation of modelled protein structure of the catecholate siderophore receptor CirA. Predicted changes in the architecture of the siderophore receptor in lateral view (left) and top view (right) are coloured in transparent gray. BDH, Neurorehabilitation centre in Greifswald; EE, experimental evolution; FDC, cefiderocol; MIC, minimum inhibitory concentration; n.a., not applicable; R, resistant; S, susceptible; UKSH, University Medical Centre Schleswig-Holstein; UMG, University Medicine Greifswald.

Data availability

The data from this study have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB63064. Additional data from the outbreak strains (PBIO1953, PBIO1961, PBIO2002, PBIO2003, PBIO2004, PBIO2005, and PBIO2006) and porin mutants derived from PBIO2003 (2003.2 and 2003.9) are available under accession numbers PRJEB37933 and PRJEB48690, respectively.